Department of Neurological Surgery, Columbia University, New York, NY, USA.
Transl Stroke Res. 2011 Sep;2(3):399-403. doi: 10.1007/s12975-011-0084-2. Epub 2011 May 17.
Dehydroascorbic acid (DHA), a blood-brain barrier transportable form of ascorbic acid, confers robust neuroprotection following murine stroke. In an effort to translate this promising neuroprotective strategy into human clinical trial, we evaluated postischemic DHA administration in a large-animal stroke model. Thirty-six adult male baboons were initially randomized to undergo transorbital craniectomy to induce transient cerebral artery occlusion and to receive postischemic dosing of either 500 mg/kg of DHA or vehicle. Primary outcomes included infarct volume, determined by magnetic resonance imaging, as well as neurological function evaluated on the day of sacrifice. The midpoint interim analysis (n = 9 per cohort) revealed that DHA administration did not significantly improve either infarct volume or neurological function. The study was terminated after a determination of statistical futility. We were unable to confirm a neuroprotective effect for postischemic DHA administration in our large-animal model using a dosing scheme that was previously successful in rodents. Further analysis of the efficacy of DHA administration must thus be undertaken prior to clinical translation.
脱氢抗坏血酸（DHA）是一种可穿透血脑屏障的抗坏血酸形式，可在小鼠中风后提供强大的神经保护作用。为了将这一有前途的神经保护策略转化为人类临床试验，我们在大动物中风模型中评估了缺血后 DHA 的给药。36 只成年雄性狨猴最初被随机分为两组，一组接受经眶颅切开术以诱导短暂性大脑中动脉闭塞，并接受 500mg/kg 的 DHA 或载体的缺血后给药；另一组则接受经眶颅切开术以诱导短暂性大脑中动脉闭塞，并接受 500mg/kg 的 DHA 或载体的缺血后给药。主要结局包括通过磁共振成像确定的梗死体积，以及在处死当天评估的神经功能。中点中期分析（每组 9 只）表明，DHA 给药并未显著改善梗死体积或神经功能。在确定统计无效后，该研究终止。我们未能在我们的大动物模型中确认缺血后 DHA 给药的神经保护作用，因为之前在啮齿动物模型中成功的给药方案在此未能发挥作用。因此，在进行临床转化之前，必须进一步分析 DHA 给药的疗效。
